This invention relates to a novel compound particularly useful as an antibiotic substance. It is most useful for treatment of coccidiosis.
Coccidiosis is a known problem for fowl, particularly chickens and turkey. There is therefore a continuing need for development of anticoccidiosis agents.
Two of the most common anticoccidiosis compounds now in use are Coban.RTM. and Salinomycin.RTM.. These compounds while effective have a high degree of toxicity. In particular it is desirable to have an antibiotic which is effective not only as an anticoccidial agent but also has low levels of toxicity in comparison with the anticoccidials currently available, namely Coban and Salinomycin.
The primary objective of the present invention is to fulfill the above-described need for an effective anticoccidial agent which has low toxicity in comparison with those commercially available.
Another objective of the present invention is to provide an improved anticoccidial agent by a simple direct synthesis route which provides a mixture of an enantiomers as opposed to a single enantiomer which might be obtained by fermentation synthesis.
The method and means of accomplishing each of the above objectives will become apparent from the detailed description which follows. The novel compound of the present invention has the formula: ##STR1##
This novel compound has valuable anticoccidial agent properties and in addition provides low levels of toxicity in comparison with presently available commercial anticoccidial agents.
In use in the present invention the compound may be used for treatment of fowl at dosage levels of from 50 parts per million to 150 parts per million, preferably at levels from about 90 parts per million to 110 parts per million. The compound may be added to pre-mix at a weight level sufficient to achieve the weights on a part per million basis as above expressed. It is then homogeneously intermixed with the feed ration and then fed to the animals.
The most closely related known structure of the present compound is frenolicin B as described in U.S. Pat. No. 4,199,514, issued Apr. 22, 1980. Frenolicin B is a different compound having a hydroxyl moiety in position 7 whereas the present claimed compound only has hydrogen in this position. Moreover, the frenolicin B of the description of U.S. Pat. No. 4,199,514 is prepared by a fermentation process by cultivating the microorganism belonging to the genus Streptomyces. Frenolicin B is a single enantiomer prepared by fermentation whereas the compound of the present invention is a mixture of enantiomers prepared by synthesis.
In accordance with the process of the present invention there are essentially three steps. In the first step there is oxidation of a hydroquinone followed by addition of a furan. In the second step, the product of the first step reaction is again oxidized to turn the intermediate phenol product into a second quinone with the lactone ring attached. And in the third and final step of the reaction there is deoxygenation, which removes the hydroxyl group to give the desired pyranoquinone of the present invention. The details of the process are set forth in the descriptive example which follows hereinafter.
Importantly the reaction is a straight forward three-step synthesis, yielding the final product in overall yields, i.e. as much as 48 percent. The reaction does not need unusual conditions. As earlier stated, pressure, etc. do not appear to be critical.
The following examples are offered to further illustrate but not limit the process and product of the present invention.